Mycofumigation by the Volatile Organic Compound-Producing Fungus Muscodor albus Induces Bacterial Cell Death through DNA Damage
Mycofumigation by the Volatile Organic Compound-Producing Fungus Muscodor albus Induces Bacterial Cell Death through DNA Damage
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DOI：
10.1128/aem.03294-14
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发表时间：
2015-02-01
影响因子：
4.4
通讯作者：
Strobela, Scott A.
中科院分区：
文献类型：
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作者：
Alpha, Cambria J.;Campos, Manuel;Strobela, Scott A.
白僵菌属于内生真菌的一个属，通过产生一种复杂的挥发性有机化合物(VOC)混合物来抑制和杀死其他真菌、细菌和昆虫。这种真菌熏蒸过程已经在商业上应用于控制人类和植物的病原体，但VOC毒性的机理尚不清楚。在这里，通过一系列的遗传筛选和生化分析来研究这些挥发物的作用方式。单基因敲除筛选表明，在暴露于白色分枝杆菌挥发性有机化合物时，缺乏DNA修复、DNA代谢过程和应激反应途径的大肠杆菌具有高度的敏感性。此外，参与特定DNA烷基加合物修复的基因敲除的敏感性表明，VOCs可能诱导烷基化。DNA损伤的证据表明，如果没有得到适当的修复，这些加合物会导致DNA复制或转录过程中的断裂。额外的细胞毒性分析表明，在VOC暴露期间，大肠杆菌变成丝状，并显示细胞膜流动性增加。白色分枝杆菌产生的有毒化合物的挥发性及其广泛的抑制作用使该真菌成为一种有吸引力的生物制剂。了解抗菌效果和挥发性有机化合物的作用模式将为白色微囊藻潜在的真菌熏蒸应用的实用性和安全性提供信息。
Muscodor albus belongs to a genus of endophytic fungi that inhibit and kill other fungi, bacteria, and insects through production of a complex mixture of volatile organic compounds (VOCs). This process of mycofumigation has found commercial application for control of human and plant pathogens, but the mechanism of the VOC toxicity is unknown. Here, the mode of action of these volatiles was investigated through a series of genetic screens and biochemical assays. A single-gene knockout screen revealed high sensitivity for Escherichia coli lacking enzymes in the pathways of DNA repair, DNA metabolic process, and response to stress when exposed to the VOCs of M. albus. Furthermore, the sensitivity of knockouts involved in the repair of specific DNA alkyl adducts suggests that the VOCs may induce alkylation. Evidence of DNA damage suggests that these adducts lead to breaks during DNA replication or transcription if not properly repaired. Additional cytotoxicity profiling indicated that during VOC exposure, E. coli became filamentous and demonstrated an increase in cellular membrane fluidity. The volatile nature of the toxic compounds produced by M. albus and their broad range of inhibition make this fungus an attractive biological agent. Understanding the antimicrobial effects and the VOC mode of action will inform the utility and safety of potential mycofumigation applications for M. albus.